The overall objective for this NCDDG application is to evaluate different methods for efficient delivery to toxin genes as a gene therapy approach for Acquired Immune Deficiency Syndrome (AIDS). Plasmid and retroviral constructs were previously generated from which toxin gene expression was controlled by HIV-1 regulatory proteins Tat and Rev. Stable cell lines were derived which had been transfected or infected with DT-A-encoding plasmids or retroviruses, respectively. Such cell lines were markedly impaired in their ability to be infected by laboratory to improve the efficiency of transfection of the toxin gene. (Project 9001) will serve as an animal core, to evaluate the in vivo anti-HIV effectiveness of toxin genes, delivered by methods described in Projects 1-2. The experiments described here should lead directly to preclinical safety and toxicity studies for HIV- regulated toxin genes. Ultimately, we hope HIV regulated toxin gene expression can be developed as a therapy for AIDS, where the immune system would be reconstituted with self-renewing, immune-competent cells which are resistant to HIV infection.